Interindividual differences in aronia juice tolerability linked to gut microbiome and metabolome changes-secondary analysis of a randomized placebo-controlled parallel intervention trial.

BACKGROUND: Aronia melanocarpa is a berry rich in polyphenols known for health benefits. However, the bioavailability of polyphenols has been questioned, and the individual taste acceptance of the fruit with its specific flavor varies. We recently observed substantial differences in the tolerability of aronia juice among healthy females, with half of the individuals tolerating aronia juice without complaints. Given the importance of the gut microbiome in food digestion, we investigated in this secondary analysis of the randomized placebo-controlled parallel intervention study (ClinicalTrials.gov registration: NCT05432362) if aronia juice tolerability was associated with changes in intestinal microbiota and bacterial metabolites, seeking for potential mechanistic insights into the impact on aronia polyphenol tolerance and metabolic outcomes. RESULTS: Forty females were enrolled for this 6-week trial, receiving either 100 ml natural aronia juice (verum, V) twice daily or a polyphenol-free placebo (P) with a similar nutritional profile, followed by a 6-week washout. Within V, individuals were categorized into those who tolerated the juice well (Vt) or reported complaints (Vc). The gut microbiome diversity, as analyzed by 16S rRNA gene-based next-generation sequencing, remained unaltered in Vc but changed significantly in Vt. A MICOM-based flux balance analysis revealed pronounced differences in the 40 most predictive metabolites post-intervention. In Vc carbon-dioxide, ammonium and nine O-glycans were predicted due to a shift in microbial composition, while in Vt six bile acids were the most likely microbiota-derived metabolites. NMR metabolomics of plasma confirmed increased lipoprotein subclasses (LDL, VLDL) post-intervention, reverting after wash out. Stool samples maintained a stable metabolic profile. CONCLUSION: In linking aronia polyphenol tolerance to gut microbiota-derived metabolites, our study explores adaptive processes affecting lipoprotein profiles during high polyphenol ingestion in Vt and examines effects on mucosal gut health in response to intolerance to high polyphenol intake in Vc. Our results underpin the importance of individualized hormetic dosing for beneficial polyphenol effects, demonstrate dynamic gut microbiome responses to aronia juice, and emphasize personalized responses in polyphenol interventions.

Probiotic, prebiotic, synbiotic and fermented food supplementation in psychiatric disorders: A systematic review of clinical trials.

The use of probiotics, prebiotics, synbiotics or fermented foods can modulate the gut-brain axis and constitute a potentially therapeutic intervention in psychiatric disorders. This systematic review aims to identify current evidence regarding these interventions in the treatment of patients with DSM/ICD psychiatric diagnoses. Forty-seven articles from 42 studies met the inclusion criteria. Risk of bias was assessed in all included studies. Major depression was the most studied disorder (n = 19 studies). Studies frequently focused on schizophrenia (n = 11) and bipolar disorder (n = 5) and there were limited studies in anorexia nervosa (n = 4), ADHD (n = 3), Tourette (n = 1), insomnia (n = 1), PTSD (n = 1) and generalized anxiety disorder (n = 1). Except in MDD, current evidence does not clarify the role of probiotics and prebiotics in the treatment of mental illness. Several studies point to an improvement in the immune and inflammatory profile (e.g. CRP, IL6), which may be a relevant mechanism of action of the therapeutic response identified in these studies. Future research should consider lifestyle and dietary habits of patients as possible confounders that may influence inter-individual treatment response.

Training in neuropsychiatry: views of early career psychiatrists from across the world.

BACKGROUND: Training and practice in neuropsychiatry varies across the world. However, little is known about the experiences and opinions of early career psychiatrists (ECPs) across different countries regarding neuropsychiatry. AIMS AND METHOD: To investigate neuropsychiatry training experiences, practices and opinions among ECPs across different countries. An online survey was distributed to ECPs in 35 countries across the world. RESULTS: A total of 522 participants took part in this study. Responses show that neuropsychiatry is integrated to a variable extent in psychiatric training curricula across the world. Most respondents were not aware of the existence of neuropsychiatric training or of neuropsychiatric units. Most agreed that training in neuropsychiatry should be done during or after the psychiatry training period. Lack of interest among specialty societies, lack of time during training, and political and economic reasons are regarded as the main barriers. CLINICAL IMPLICATIONS: These findings call for an improvement in the extent and in the quality of neuropsychiatry training across the world.

Impaired implicit learning in adults with anorexia nervosa.

OBJECTIVE: Cognitive alterations play an important role in the pathophysiology and treatment of anorexia nervosa (AN). Previous studies suggest that some implicit learning processes may be inhibited in AN. However, this has not yet been fully explored. The purpose of this study is to analyze implicit learning in patients with AN in comparison to healthy controls. METHODS: In this pilot-study, a total of 21 patients diagnosed with AN and 21 matched controls were administered the weather prediction task (WPT), a probabilistic implicit category learning task that consists of two sub-variants. During the feedback (FB) version of the task, participants learn associations between tarot cards and weather outcomes via an operant learning model through which they receive immediate FB on their answers, whereas during the paired associate (PA) variant, participants are directly asked to memorize given associations. RESULTS: AN patients showed selective impairment on the FB task where they scored significantly lower both in comparison to controls (p = .001) who completed the same task and when compared to their own performance on the PA variant (p = .006). Clinical measures showed no significant correlations with test scores. DISCUSSION: Our results demonstrate implicit FB learning deficiencies in adult patients with AN. These impairments may have an impact on the effect of psychotherapeutic interventions and could partially explain the lack of treatment response in AN. Further studies are necessary to derive when and through which mechanisms these alterations originate, and to what extent they should be considered during treatment of the disorder. PUBLIC SIGNIFICANCE: Cognitive impairments pose a challenge in the management of anorexia nervosa. Improved comprehension of cognitive alterations could lead to a greater understanding of the disease and adaptation of psychotherapeutic treatments. In this study, we found that implicit feedback learning in anorexia nervosa is impaired compared to healthy controls. This could indicate the necessity of treatment adaptations in the form of therapy tools without feedback and a larger focus on psychoeducation.

Attitudes of psychiatrists towards people with mental illness: a cross-sectional, multicentre study of stigma in 32 European countries.

Background: Mental health-related stigma occurs among the public and professionals alike. The lived experience of mental illness has been linked to less stigmatising attitudes. However, data on psychiatrists and the relationship between stigmatising attitudes and psychotherapeutic activity or case discussion groups remains scarce. Methods: A cross-sectional multicentre study was performed in 32 European countries to investigate the lived experiences and attitudes of psychiatrists toward patients with mental illness as well as the relationship between stigma, psychosocial and professional factors. The self-reported, anonymous, internet-based Opening Minds Stigma Scale for Health Care Providers was used to measure the stigmatising attitudes. The survey was translated into the local language of each participating country. All participants were practising specialists and trainees in general adult or child and adolescent psychiatry. The study took place between 2nd October, 2019 and 9th July, 2021 and was preregistered at ClinicalTrial.gov (NCT04644978). Findings: A total of 4245 psychiatrists completed the survey. The majority, 2797 (66%), had completed training in psychiatry, and 3320 (78%) worked in adult psychiatry. The final regression model showed that across European countries more favourable attitudes toward people with mental illness were statistically significantly associated with the lived experience of participants (including seeking help for their own mental health conditions (d = -0.92, 95% confidence interval (CI) = -1.68 to -0.15, p = 0.019), receiving medical treatment for a mental illness (d = -0.88, 95% CI = -1.71 to -0.04, p = 0.040), as well as having a friend or a family member similarly affected (d = -0.68, 95% CI = -1.14 to -0.22, p = 0.004)), being surrounded by colleagues who are less stigmatising (d = -0.98, 95% CI = -1.26 to -0.70, p < 0.001), providing psychotherapy to patients (d = -1.14, 95% CI = -1.63 to -0.65 p < 0.001), and being open to (d = -1.69, 95% CI = -2.53 to -0.85, p < 0.001) and actively participating in (d = -0.94, 95% CI = -1.45 to -0.42, p < 0.001) case discussion, supervision, or Balint groups. Interpretation: Our study highlights the importance of psychotherapy training, supervision, case discussions and Balint groups in reducing the stigmatising attitudes of psychiatrists toward patients. As the findings represent cross-national predictors, Europe-wide policy interventions, national psychiatric education systems and the management of psychiatric institutions should take these findings into consideration. Funding: National Youth Talent Award (Ministry of Human Resources, Hungary, (NTP-NFTÖ-20-B-0134). All authors received no funding for their contribution.

The Association of Tube Weaning and Oral Skill Development in Infants With Tube Dependency: A Prospective Study.

OBJECTIVE: This study was the first of its kind by assessing oral skills development during and after applying the "Graz Model" of tube weaning. METHODS: This prospective case series study included data of 67 (35 females, 32 males, treated from March 2018 to April 2019) tube dependent children, who participated in the effective "Graz Model" of tube weaning. Parents filled out the standardized Pediatric Assessment Scale for Severe Feeding Problems (PASSFP) prior to and immediately after completion of the program. Paired sample t tests were conducted to examine pre-to-post changes in the children's oral skills. RESULTS: The study showed that oral skills increased significantly during tube weaning PASSFP score of 24.76 (standard deviation, SD = 12.38) prior to versus 47.97 (SD = 6.98) after completion of the program. Furthermore, significant changes in their sensory and tactile perception and in their general eating behavior were observed. Children also showed reduced oral aversion symptoms and food pocketing, could enjoy their meals, and increased their food repertoire. Mealtime duration could be decreased, and parents were less anxious about their infants' intake and less frustrated because of their children's eating behavior. CONCLUSION: The results of this study demonstrated for the first time that tube dependent children can improve their oral skills significantly during and after their participation in the child-led approach of the "Graz model" of tube weaning.

Gut Microbiome Composition and Its Association with Sleep in Major Psychiatric Disorders.

INTRODUCTION: Sleep disturbances are highly prevalent across most major psychiatric disorders. Alterations in the hypothalamic-pituitary-adrenal axis, neuroimmune mechanisms, and circadian rhythm disturbances partially explain this connection. The gut microbiome is also suspected to play a role in sleep regulation, and recent studies suggest that certain probiotics, prebiotics, synbiotics, and fecal microbiome transplantation can improve sleep quality. METHODS: We aimed to assess the relationship between gut-microbiota composition, psychiatric disorders, and sleep quality in this cross-sectional, cross-disorder study. We recruited 103 participants, 63 patients with psychiatric disorders (major depressive disorder [n = 31], bipolar disorder [n = 13], psychotic disorder [n = 19]) along with 40 healthy controls. Sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI). The fecal microbiome was analyzed using 16S rRNA sequencing, and groups were compared based on alpha and beta diversity metrics, as well as differentially abundant species and genera. RESULTS: A transdiagnostic decrease in alpha diversity and differences in beta diversity indices were observed in psychiatric patients, compared to controls. Correlation analysis of diversity metrics and PSQI score showed no significance in the patient and control groups. However, three species, Ellagibacter isourolithinifaciens, Senegalimassilia faecalis, and uncultured Blautia sp., and two genera, Senegalimassilia and uncultured Muribaculaceae genus, were differentially abundant in psychiatric patients with good sleep quality (PSQI >8), compared to poor-sleep quality patients (PSQI ≤8). CONCLUSION: In conclusion, this study raises important questions about the interconnection of the gut microbiome and sleep disturbances.

Psychometric properties of the Opening Minds Stigma Scale for Health Care Providers in 32 European countries - A bifactor ESEM representation.

Aims: To measure the stigma of healthcare providers toward people suffering from mental illness, the Opening Minds Stigma Scale for Health Care Providers (OMS-HC) is a commonly applied instrument. However, this scale has not been thoroughly validated in many European countries, its psychometric properties are still unknown and data on practicing psychiatrists is lacking. Therefore, this multicenter study aimed to assess the psychometric characteristics of the 15-item OMS-HC in trainees and specialists in adult and child psychiatry in 32 countries across Europe. Materials and methods: The OMS-HC was conducted as an anonymous online survey and sent via Email to European adult and child psychiatrists. Parallel analysis was used to estimate the number of OMS-HC dimensions. Separate for each country, the bifactor ESEM, a bifactor exploratory structural equation modeling approach, was applied to investigate the factor structure of the scale. Cross-cultural validation was done based on multigroup confirmatory factor analyses and reliability measures. Results: A total of 4,245 practitioners were included, 2,826 (67%) female, 1,389 (33%) male. The majority (66%) of participants were specialists, with 78% working in adult psychiatry. When country data were analyzed separately, the bifactor model (higher-order factor solution with a general factor and three specific factors) showed the best model fit (for the total sample χ2/df = 9.760, RMSEA = 0.045 (0.042-0.049), CFI = 0.981; TLI = 0.960, WRMR = 1.200). The average proportion of variance explained by the general factor was high (ECV = 0.682). This suggests that the aspects of 'attitude,' 'disclosure and help-seeking,' and 'social distance' could be treated as a single dimension of stigma. Among the specific factors, the 'disclosure and help-seeking' factor explained a considerable unique proportion of variance in the observed scores. Conclusion: This international study has led to cross-cultural analysis of the OMS-HC on a large sample of practicing psychiatrists. The bifactor structure displayed the best overall model fit in each country. Rather than using the subscales, we recommend the total score to quantify the overall stigmatizing attitudes. Further studies are required to strengthen our findings in countries where the proposed model was found to be weak.

Thinking beyond Vaccination: Promising Add-On Strategies to Active Immunization and Vaccination in Pandemics-A Mini-Review.

There is little doubt that final victories over pandemics, such as COVID-19, are attributed to herd immunity, either through post-disease convalescence or active immunization of a high percentage of the world's population with vaccines, which demonstrate protection from infection and transmission and are available in large quantities at reasonable prices. However, it is assumable that humans with immune defects or immune suppression, e.g., as a consequence of allograft transplantation, cannot be immunized actively nor produce sufficient immune responses to prevent SARS-CoV-2 infections. These subjects desperately need other strategies, such as sophisticated protection measures and passive immunization. Hypertonic salt solutions attack vulnerable core areas of viruses; i.e., salt denatures surface proteins and thus prohibits virus penetration of somatic cells. It has to be ensured that somatic proteins are not affected by denaturation regarding this unspecific virus protection. Impregnating filtering facepieces with hypertonic salt solutions is a straightforward way to inactivate viruses and other potential pathogens. As a result of the contact of salt crystals on the filtering facepiece, these pathogens become denatured and inactivated almost quantitatively. Such a strategy could be easily applied to fight against the COVID-19 pandemic and other ones that may occur in the future. Another possible tool to fight the COVID-19 pandemic is passive immunization with antibodies against SARS-CoV-2, preferably from human origin. Such antibodies can be harvested from human patients' sera who have successfully survived their SARS-CoV-2 infection. The disadvantage of a rapid decrease in the immunoglobulin titer after the infection ends can be overcome by immortalizing antibody-producing B cells via fusion with, e.g., mouse myeloma cells. The resulting monoclonal antibodies are then of human origin and available in, at least theoretically, unlimited amounts. Finally, dry blood spots are a valuable tool for surveilling a population's immunity. The add-on strategies were selected as examples for immediate, medium and long-term assistance and therefore did not raise any claim to completeness.

The Muscle-Gut-Brain Axis and Psychiatric Illness.

The microbiota-gut-brain axis (MGBA) has been the subject of much research over the past decade, offering an exciting new paradigm for the treatment of psychiatric disorders. In this review, the MGBA is extended to include skeletal muscle and the potential role of an expanded "muscle-gut-brain axis" (MuGBA) in conditions such as anxiety and depression is discussed. There is evidence, from both preclinical and human studies, of bidirectional links between the gut microbiome and skeletal muscle function and structure. The therapeutic role of exercise in reducing depressive and anxiety symptoms is widely recognised, and the potential role of the gut microbiota-skeletal muscle link is discussed within this context. Potential pathways of communication involved in the MuGBA including the tryptophan-kynurenine pathway, intestinal permeability, immune modulation, and bacterial metabolites such as short-chain-fatty-acids are explored.

The gut microbiome in social anxiety disorder: evidence of altered composition and function.

The microbiome-gut-brain axis plays a role in anxiety, the stress response and social development, and is of growing interest in neuropsychiatric conditions. The gut microbiota shows compositional alterations in a variety of psychiatric disorders including depression, generalised anxiety disorder (GAD), autism spectrum disorder (ASD) and schizophrenia but studies investigating the gut microbiome in social anxiety disorder (SAD) are very limited. Using whole-genome shotgun analysis of 49 faecal samples (31 cases and 18 sex- and age-matched controls), we analysed compositional and functional differences in the gut microbiome of patients with SAD in comparison to healthy controls. Overall microbiota composition, as measured by beta-diversity, was found to be different between the SAD and control groups and several taxonomic differences were seen at a genus- and species-level. The relative abundance of the genera Anaeromassillibacillus and Gordonibacter were elevated in SAD, while Parasuterella was enriched in healthy controls. At a species-level, Anaeromassilibacillus sp An250 was found to be more abundant in SAD patients while Parasutterella excrementihominis was higher in controls. No differences were seen in alpha diversity. In relation to functional differences, the gut metabolic module 'aspartate degradation I' was elevated in SAD patients. In conclusion, the gut microbiome of patients with SAD differs in composition and function to that of healthy controls. Larger, longitudinal studies are warranted to validate these preliminary results and explore the clinical implications of these microbiome changes.

Advances in the gut microbiome and mood disorders.

PURPOSE OF REVIEW: The gut microbiome is in constant bidirectional communication with the brain through the microbiota-gut-brain-axis. Mood disorders are among the most common psychiatric disorders and include major depressive disorder and bipolar disorder. The gut microbiome is altered in individuals with mood disorders and has a role in its inflammatory pathophysiology. In this article, we performed a narrative review of clinical studies, randomized controlled trials and meta-analyses addressing advances in gut microbiome research in mood disorders and included articles that were published between 2021 and 2022. RECENT FINDINGS: Studies highlight transdiagnostic alterations of microbiota in mood disorders, with reductions of butyrate-producing bacteria. Participants with major depressive disorder showed altered beta-diversity, while participants with bipolar disorder showed reduced alpha-diversity. Both disorders exhibit alterations in the metabolome. Early pilot studies addressed the possibility of using the gut microbiome for the prediction of treatment response and the blood microbiome for the diagnosis of psychiatric disorders. Findings from clinical trials support the use of probiotics as an add-on therapy for major depressive disorder. The second published case report in the literature reported a favourable outcome of a patient with bipolar disorder after faecal microbiota transplantation. SUMMARY: Gut microbiome modulations allow new treatment strategies including the use of psychobiotics for the treatment and prevention of mood disorders. Well designed clinical trials aiming for personalized medicine are needed to investigate the efficacy and safety of psychobiotic interventions.

Cardiac vagal activity is associated with gut-microbiome patterns in women-An exploratory pilot study.

Introduction: A functional reciprocity between the gut microbiome and vagal nerve activity has been suggested, however, human studies addressing this phenomenon are limited. Methods: Twenty-four-hour cardiac vagal activity (CVA) was assessed from 73 female participants (aged 24.5 ± 4.3 years). Additionally, stool samples were subjected to 16SrRNA gene analysis (V1-V2). Quantitative Insights Into Microbial Ecology (QIIME) was used to analyse microbiome data. Additionally, inflammatory parameters (such as CRP and IL-6) were derived from serum samples. Results: Daytime CVA correlated significantly with gut microbiota diversity (r sp = 0.254, p = 0.030), CRP (r sp = -0.348, p = 0.003), and IL-6 (r sp = -0.320, p = 0.006). When the group was divided at the median of 24 h CVA (Mdn = 1.322), the following features were more abundant in the high CVA group: Clostridia (Linear discriminant analysis effect size (LDA) = 4.195, p = 0.029), Clostridiales (LDA = 4.195, p = 0.029), Lachnospira (LDA = 3.489, p = 0.004), Ruminococcaceae (LDA = 4.073, p = 0.010), Faecalibacterium (LDA = 3.982, p = 0.042), Lactobacillales (LDA = 3.317, p = 0.029), Bacilli (LDA = 3.294, p = 0.0350), Streptococcaceae (LDA = 3.353, p = 0.006), Streptococcus (LDA = 3.332, p = 0.011). Based on Dirichlet multinomial mixtures two enterotypes could be detected, which differed significantly in CVA, age, BMI, CRP, IL-6, and diversity. Conclusions: As an indicator of gut-brain communication, gut microbiome analysis could be extended by measurements of CVA to enhance our understanding of signalling via microbiota-gut-brain-axis and its alterations through psychobiotics.

The PROVIT Study-Effects of Multispecies Probiotic Add-on Treatment on Metabolomics in Major Depressive Disorder-A Randomized, Placebo-Controlled Trial.

The gut-brain axis plays a role in major depressive disorder (MDD). Gut-bacterial metabolites are suspected to reduce low-grade inflammation and influence brain function. Nevertheless, randomized, placebo-controlled probiotic intervention studies investigating metabolomic changes in patients with MDD are scarce. The PROVIT study (registered at clinicaltrials.com NCT03300440) aims to close this scientific gap. PROVIT was conducted as a randomized, single-center, double-blind, placebo-controlled multispecies probiotic intervention study in individuals with MDD (n = 57). In addition to clinical assessments, metabolomics analyses (1H Nuclear Magnetic Resonance Spectroscopy) of stool and serum, and microbiome analyses (16S rRNA sequencing) were performed. After 4 weeks of probiotic add-on therapy, no significant changes in serum samples were observed, whereas the probiotic groups' (n = 28) stool metabolome shifted towards significantly higher concentrations of butyrate, alanine, valine, isoleucine, sarcosine, methylamine, and lysine. Gallic acid was significantly decreased in the probiotic group. In contrast, and as expected, no significant changes resulted in the stool metabolome of the placebo group. Strong correlations between bacterial species and significantly altered stool metabolites were obtained. In summary, the treatment with multispecies probiotics affects the stool metabolomic profile in patients with MDD, which sets the foundation for further elucidation of the mechanistic impact of probiotics on depression.

Immunomodulatory Effects of Aronia Juice Polyphenols-Results of a Randomized Placebo-Controlled Human Intervention Study and Cell Culture Experiments.

Dietary polyphenols, which are present in Aronia melanocarpa, have been associated with various beneficial effects on human health including antioxidant, antiviral, and anti-inflammatory activities. We aimed to investigate the immunomodulatory effects of aronia juice polyphenols in a randomized placebo-controlled human intervention study and cell culture experiments. A total of 40 females were asked to consume either 200 mL of aronia juice or a placebo drink for six weeks and were investigated again after a washout period of another six weeks. We observed that only half of the participants tolerated the aronia juice well (Vt) and the other half reported complaints (Vc). The placebo (P) was generally tolerated with one exception (p = 0.003). Plasma polyphenol levels increased significantly in Vt after the intervention (p = 0.024) but did neither in P nor in Vc. Regulatory T cell (Treg) frequencies remained constant in Vt and P during the intervention, whereas Tregs decreased in Vc (p = 0.018). In cell culture, inhibiting effects of ferulic acid (p = 0.0005) and catechin (p = 0.0393) on the differentiation of Tregs were observed as well as reduced activation of CD4-T cells in ferulic acid (p = 0.0072) and aronia juice (p = 0.0163) treated cells. Interestingly, a CD4+CD25-FoxP3+ cell population emerged in vitro in response to aronia juice, but not when testing individual polyphenols. In conclusion, our data strengthen possible individual hormetic effects, the importance of the food matrix for bioactivity, and the need for further investigations on possible impacts of specific physiological features such as the gut microbiota in the context of personalized nutrition.

Oxidative Status in Adult Anorexia Nervosa Patients and Healthy Controls-Results from a Cross-Sectional Pilot Study.

Oxidative stress describes an imbalance of reactive oxygen species (ROS) and antioxidative defence systems. Recently, the consequences of oxidative stress have become a central field of research and have been linked to the genesis of multiple psychiatric diseases. Some oxidative stress parameters have not been investigated before in anorexia nervosa (AN) patients, including the gut microbiota-derived metabolite trimethylamine N-oxide (TMAO) and polyphenols (PPm). In this cross-sectional pilot study, we evaluated these markers together with total peroxides (TOC), antioxidative capacity (TAC), endogenous peroxidase activity (EPA) and antibodies against oxidized LDL (oLAb) in serum samples of 20 patients with AN compared to 20 healthy controls. The antioxidative capacity was significantly decreased in AN patients, with a mean TAC of 1.57 mmol/L (SD: ±0.62); t (34) = -2.181, p = 0.036) compared to HC (mean = 1.91 mmol/L (SD: ±0.56), while the other investigated parameters were not significantly different between the two groups. In AN patients, TAC correlated with EPA (rsp = -0.630, p = 0.009). This study suggests that there is an antioxidative deficiency in AN patients. In this respect, there is a demand for interventional studies to determine whether antioxidants can be used as add-on therapy in the treatment of AN.

Anorexia Nervosa Is Associated with a Shift to Pro-Atherogenic Low-Density Lipoprotein Subclasses.

Anorexia nervosa (AN) is a severe eating disorder affecting primarily female adolescents and younger adults. The energy deprivation associated with AN has been shown to alter lipoprotein metabolism, which may affect cardiovascular risk. However, the mechanisms leading to alterations in the composition, structure, and function of lipoproteins in AN patients are not well-understood yet. Here, we investigated the lipid abnormalities associated with AN, particularly changes in the distribution, composition, metabolism, and function of lipoprotein subclasses. In this exploratory study, we analyzed serum samples of 18 women diagnosed with AN (BMI < 17.5 kg/m2) and 24 normal-weight women (BMI from 18.5−24.9 kg/m2). Using the Quantimetrix Lipoprint® system, we determined low-density lipoprotein (LDL) subclass distribution, including quantitative measurements of very low-density lipoprotein (VLDL), intermediate density lipoprotein (IDL) and high-density lipoprotein (HDL) subclass distribution. We quantified the most abundant apolipoproteins of HDL and assessed lecithin-cholesterol acyltransferase (LCAT) and cholesteryl-ester transfer protein (CETP) activities. In addition, anti-oxidative capacity of apoB-depleted serum and functional metrics of HDL, including cholesterol efflux capacity and paraoxonase activity were assessed. The atherogenic lipoprotein subclasses VLDL and small LDL particles were increased in AN. Levels of VLDL correlated significantly with CETP activity (rs = 0.432, p = 0.005). AN was accompanied by changes in the content of HDL-associated apolipoproteins involved in triglyceride catabolism, such as apolipoprotein C-II (+24%) and apoA-II (−27%), whereas HDL-associated cholesterol, phospholipids, and triglycerides were not altered. Moreover, AN did not affect HDL subclass distribution, cholesterol efflux capacity, and paraoxonase activity. We observed a shift to more atherogenic lipoprotein subclasses in AN patients, whereas HDL functionality and subclass distribution were not altered. This finding underpins potential detrimental effects of AN on lipid metabolism and the cardiovascular system by increasing atherosclerotic risk factors.

Preliminary Assessment of Pre-Electroconvulsive Therapy Evaluation Practices in European Countries: The Need for Guidelines.

OBJECTIVES: Pre-electroconvulsive therapy (ECT) evaluation is an essential part of ECT preparation, a standard treatment in the psychiatric field. However, no routine pre-ECT evaluation has been published so far. This preliminary study aimed to explore different practices in pre-ECT evaluation across European countries. METHODS: The data were collected as a snowball sample approach using an online survey from September 2019 to April 2020. The final analysis included data from 18 clinics placed in 16 European countries. RESULTS: Regulations on the pre-ECT evaluation were found in 9 countries. All clinics reported doing complete blood count, serum electrolytes, and renal function analysis as a part of regular laboratory testing, alongside with a cardiovascular assessment. Ten clinics reported using psychiatric scales. Six clinics reported doing a cognitive assessment, of which all had regulations on the pre-ECT evaluation. Not one evaluation had the same sets of procedures and diagnostics. CONCLUSIONS: The differences in assessment approaches mirror high variability of the pre-ECT evaluation practice across Europe. Cognitive assessment and objectification of psychiatric symptoms should be a regular part of the pre-ECT evaluation because of the monitoring of the most common adverse effect and observing the clinical response to ECT. Standardization of the pre-ECT evaluation and ECT in general would remove criticisms and opposition to the treatment, make it based on the best of our knowledge, and provide a method respectful of patients' best interests and rights.

The immune-kynurenine pathway in social anxiety disorder.

BACKGROUND: The tryptophan-kynurenine pathway is of major interest in psychiatry and is altered in patients with depression, schizophrenia and panic disorder. Stress and immune alterations can impact this system, through cortisol- and cytokine-induced activation. In addition, there is emerging evidence that the kynurenine pathway is associated with suicidality. There have been no studies to date exploring the immune-kynurenine system in social anxiety disorder (SAD), and indeed very limited human studies on the kynurenine pathway in any clinical anxiety disorder. METHODS: We investigated plasma levels of several kynurenine pathway markers, including kynurenine (KYN), tryptophan (TRYP) and kynurenic acid (KYNA), along with the KYN/TRYP and KYNA/KYN ratios, in a cohort of 32 patients with SAD and 36 healthy controls. We also investigated a broad array of both basal and lipopolysaccharide (LPS)-stimulated blood cytokine levels including IFN-γ, interleukin (IL)-10, IL-1ß, IL-2, IL-4, IL-6, IL-8 and tumor necrosis factor (TNF)-α. RESULTS: SAD patients had elevated plasma KYNA levels and an increased KYNA/KYN ratio compared to healthy controls. No differences in KYN, TRYP or the KYN/TRYP ratio were seen between the two groups. SAD patients with a history of past suicide attempt showed elevated plasma KYN levels and a higher KYN/TRYP ratio compared to patients without a history of suicide attempt. No differences were seen in basal or LPS-stimulated pro-inflammatory cytokine levels between the patients and controls. However, unstimulated IL-10, an anti-inflammatory cytokine, was significantly lower in the SAD group. A significant sex influence was evident with SAD males having lower levels of IL-10 compared to healthy males but no difference seen between SAD females and healthy females. CONCLUSIONS: The peripheral kynurenine pathway is altered in SAD and preferentially directed towards KYNA synthesis. Additionally, kynurenine pathway activation, as evidenced by elevated KYN and KYN/TRYP ratio, is evident in SAD patients with a history of past suicide attempt. While no differences in pro-inflammatory cytokines is apparent in SAD patients, lower anti-inflammatory IL-10 levels are seen in SAD males. Further investigation of the role of the immune-kynurenine pathway in SAD and other clinical anxiety disorders is warranted.

The Impact of Cardiovascular Rehabilitation on Psychophysiological Stress, Personality and Tryptophan Metabolism: A Randomized Pilot Feasibility Study.

Multicomponent cardiac rehabilitation (CR) is a secondary prevention strategy for cardiac patients to tackle stress and psychosocial wellbeing. However, there is a lack of data on its psychoneuroimmunological effects and of biomarkers to determine individual risk and to develop treatment strategies. We conducted a pilot randomized controlled trial (RCT) to investigate the feasibility of deriving psychophysiological stress markers in patients with cardiovascular diseases. Thirty individuals with cardiovascular disease (mean age 58.8 years; 23.3% female) were enrolled and randomized into three treatment groups: standard rehabilitation, yoga, or transcendental meditation (TM). Depression, anxiety, sleep, stress perception, personality functioning, hair cortisol, serum tryptophan, kynurenine and neopterin concentrations were estimated at baseline and after a four-week intervention. Hair cortisol levels decreased significantly after rehabilitation in all groups (F = 15.98, p < 0.001). In addition, personality functioning improved in all patients over time. Participants with impairments in personality functioning showed a positive correlation with baseline neopterin that did not remain significant after Bonferroni correction. Concentrations of serum tryptophan and its metabolite kynurenine did not change significantly. This pilot RCT provides preliminary evidence of multicomponent CR leading to stabilization of hair cortisol levels and improved psychophysiological wellbeing and personality functioning. Impairments in personality functioning were correlated with neopterin levels, which may impact the symptomatology and outcome.